CD22 is a 135 kDa sialoglycoprotein expressed on the surface of B-cells at the mature stages of cell differentiation (Dorken et al., J. Immunol. 136:4470-4479, 1986). CD22 functions in B-cell activation and as an adhesion molecule, mediating interactions with activated blood cells and accessory cells (Hanasaki et al., J. Biol. Chem. 270(13):7533-7542, 1995). CD22 is not found on the surface of B cells during the early stages of development, nor is it expressed in stem cells. However, 60-70% of all B-cell lymphomas and leukemias express CD22.
Expression of CD22 in a number of B-cell malignancies has made CD22 an attractive target for immunotherapy. For example, Epratuzumab, a humanized anti-CD22 antibody has been evaluated in patients with aggressive non-Hodgkin's lymphoma (Leonard et al., Clin. Cancer Res. 10:5327-5334, 2004). Immunoconjugates including chimeric (humanized) anti-CD22 antibodies have also been studied, such as CMC-544 (DiJoseph et al., Clin. Cancer Res. 12(1):242-249, 2006). An anti-CD22 immunotoxin BL22, a mouse anti-CD22 antibody linked to Pseudomonas exotoxin PE38, has been evaluated for efficacy in the treatment of hairy cell leukemia (Kreitman et al., N. Engl. J. Med. 345(4):241-247; U.S. Patent Application Publication Nos. 2005/0118182 and 2007/0189962).
CD22-specific antibodies have potential as cancer therapeutic and diagnostic reagents. However, a major limitation in the clinical use of mouse monoclonal antibodies is the development of a human anti-murine antibody (HAMA) response. The HAMA response can involve allergic reactions and an increased rate of clearance of the administered antibody from the serum. A need remains for fully human antibodies that specifically bind CD22 with high affinity, which can be used in the diagnosis and treatment of cancer, particularly in the treatment of B-cell malignancies. However, it is difficult to produce fully human antibodies to human antigens, as these antigens are generally recognized as self antigens.